Is Childhood-Onset Schizophrenia Caused by Genetic or Environmental Factors?

Let’s take a look at how the developing nervous system is affected by childhood-onset schizophrenia (COS), and how genetics vs. environmental factors influence a child’s likelihood of exhibiting signs of schizophrenia in adolescence. While there is some research that explores COS, it feels like more could be done to understand the disorder from a research perspective. I think that if were able to identify traits associated with COS we may be able to begin treatment sooner, and have the ability to treat the disorder more effectively in both childhood and adult-onset patients.

An article titled Childhood Adversity and Hippocampal and Amygdala Volumes in a Population at Familial High Risk of Schizophrenia, the author claims that neurodevelopmental abnormalities in the hippocampal formation play a role in the development of schizophrenia. The author states that hypothalamic-pituitary-adrenal (HPA) axis activation is triggered by environmental stressors, and that children who are subjected to childhood adversity are at an increased risk of suffering from psychiatric disorders such as schizophrenia. The article goes on to insinuate that the enduring effects of stress during a sensitive developmental period in the hippocampus may cause injury to neurons within the hippocampus. This area of the brain plays a crucial role in the triggering of the HPA axis which indicates that these individuals are more likely to experience stress related hippocampal alterations. The author discussed a study that determined whether indicators of childhood adversity were associated with alterations of the hippocampus and amygdala. This was a descriptive research design as it relied on case-studies of social workers. Researchers would have chosen this method because it detailed children who had experienced childhood adversity, and children who were at high familial risk of schizophrenia. The author believed that the goal of the study was to combine justice and welfare for children.

According to the authors of Cognitive Correlates of Gray Matter Abnormalities in Adolescent Siblings of Patients with Childhood-Onset Schizophrenia, individuals with COS display gray matter (GM) abnormalities, and that the healthy siblings of patients with COS share some of the abnormalities. This indicates that GM abnormalities are endophenotypes for schizophrenia. The article also discusses how the corticostriatal system influences skill learning. The author goes on to say that the corticostriatal dysfunction in COS siblings is linked to deficits in cognitive skill learning. The article implies that corticostriatal and cerebellar impairments in unaffected siblings of COS patients are indicators of a genetic risk for schizophrenia. The study discussed in this article consisted of measuring structural abnormalities of the brain using volumetric brain morphometry (VBM). I believe that the researchers chose this to reflect the patterns of structural abnormalities in COS patients vs. their healthy siblings.

The 2013 article Absence of Anatomic Corpus Callosal Abnormalities in Childhood-Onset Schizophrenia Patients and Healthy Siblings argues that abnormalities of the corpus callosum were considered to be an indicator of schizophrenia. However, the author then claims that research shows there isn’t enough variance between the corpus callosum of COS patients, healthy siblings, and healthy volunteers to suggest that abnormalities of the corpus callosum are salient features indicative of schizophrenia. It is then suggested that corpus callosum deficits are commonly reported in adults with schizophrenia, so the author theorized that if the deficit could be seen in children, it would make diagnosing COS an easier task. The researchers participating in the study described in this article used 235 MRI scans from 98 COS patients, 153 scans from 71 of their healthy siblings, and 253 scans from 100 age/gender matched healthy volunteers; and the longitudinal data was examined with mixed model regression analysis.

In 1994 the Journal of Child Psychologyand Psychiatry published an article titled Childhood-Onset Schizophrenia. According to this article, COS is more likely to be a familial and more severe version of the disorder than what those who exhibit symptoms in early adulthood experience. The author of this article implied that because of their young age, findings with schizophrenic children are less likely to be influenced by comorbid factors like neuroleptic treatment or chronic institution; and the author expressed hope that current reliable systematic assessment of schizophrenic symptoms and syndromes would provide information regarding the isolation of etiological factors and pathways. While the article doesn’t focus on one specific study, the author does discuss the frequency of controversial clinical and research issues arising in relation to COS. The most common argument seems to be the possibility that childhood-onset schizophrenia and later-onset schizophrenia are not the same disorder or illness. This theory has given researchers hope that developmental psychopathology could potentially improve treatment plans outlined for children diagnosed with COS.

An article published within Archives of General Psychiatry explores the relationship between brain abnormalities, particularly ventricular volume and decreases in the midsagittal thalamic area, and the likelihood of a child being diagnosed with COS. The article describes a study in which anatomic brain MRIs were obtained for 16 children and adolescents with COS onset by 12 years of age, and 24 temporally yoked, age and sex matched healthy control subjects. The subjects were scanned once upon being approved as a participant in the study, and again 2 years later. Researchers were careful to use identical equipment and measurement methods in order to ensure that the results were accurate, and that the study was ethical. The author claims that the COS patients participating in the study showed a significantly greater increase in ventricular volume than the healthy control subjects did, and a significant decrease in the midsagittal thalamic area was also present for those with COS, but not for the healthy control subjects. The article implies that patients with COS exhibited changes of the brain that correlated significantly with each other and were commonly predicted by pre-psychotic developmental abnormalities.

Another article from Archives of General Psychology titled Brain Anatomic Magnetic Resonance Imaging in Childhood-Onset Schizophrenia discusses the rarity of studies that are focused on COS, and states that a correlation between COS biological continuity with the later-onset disorder has not been able to be established. The study focused on in this article is based on early-onset schizophrenia where the first psychotic symptoms present no later than 12 years of age. The author emphasizes that there are only a small number of these studies, and their biological continuity with later-onset schizophrenia has not been established yet. Researchers compared quantitative anatomic brain MRIs of 21 children and adolescents with early-onset schizophrenia to those of 33 matched control subjects, and the abnormalities were then compared in relation to those reported with later-onset forms of the disorder. Parts of the brain examined during the study were the cerebrum, anterior frontal region, lateral ventricles, thalamus, caudate, putamen, and globus pallidus. The research concluded that the caudate, globus pallidus, lateral ventricles, and putamen were larger in patents with early-onset schizophrenia. It was stated that the enlargement of the globus pallidus correlates with a neuroleptic exposure, and with early-onset psychosis. Compared to the healthy controls, the results were indicative of slightly smaller cerebral volumes for the participants with COS.

An article published within the Journal of the American Academy of Child & Adolescent Psychiatry explores velocardiofacial syndrome, and the rate of 22q11 deletions that are associated with patients who had experienced COS. This research is then compared to 22q11 deletions in patients with adult-onset cases of schizophrenia. The article states that the deletion of the chromosome 22q11.2 or 22q11DS is the most frequent chromosomal microdeletion found in humans. The deletion of this chromosome is thought to happen in 1 in 2,000-4,000 live births, and typically the chromosomal deletion is associated with congenital abnormalities, cognitive deficits, and major psychiatric illnesses in early childhood and adolescence. Schizophrenia spectrum disorders are normally present in about 10-25% of effected individuals; also present, but slightly less common at 10-15% are bipolar disorder and major depression. About 60% of individuals with chromosome 22q11.2 deletion syndrome are thought to have some form of psychiatric disorder, with approximately 25-40% of those being major psychiatric disorders. The article implies that children with the chromosomal deletion have deficits in attention span, executive function, and verbal skills, and those at high risk for schizophrenia typically exhibit similar deficits. The researchers associated with this study used quantitative MRI scans from children with 22q11DS that were taken prior to the onset of psychosis, and found that wide-spread gray matter reduction in the posterior and temporal cortices, the cerebellum, and the hippocampus were common in patients with COS, though there was a preservation of the frontal lobes. This loss of gray matter has long been described in individuals who are considered to be at high-risk of schizophrenia. The analysis of the brain images suggested that an enlarged cave of septum pellucidum (CSP) associated with maldevelopment of structures like the amygdala and the cingulate gyrus are found in both children with 22q11DS and adults with 22q11DS who have schizophrenia. The research was indicative of a large CSP being a marker of abnormal neurodevelopment of structures like the cingulate gyrus.

As biopsychology has grown, there have been significant advancements in technology that have influenced research on human behavior. One specific way that technology has impacted research related to human behavior is the use of MRI machines. By using these machines, we are able to see detailed pictures of the human brain, and we are able to better understand how each area of the brain influences various aspects of behavior. Historically society’s opinion of biopsychology has been generally positive. Views have shifted from seeing schizophrenia as a genetic disorder, and have begun looking at environmental factors that may play a role in triggering COS. From these references, we can conclude that COS is not solely genetic, and can be triggered by childhood adversity. We can also conclude that abnormalities of the corpus callosum are not significant enough to be deemed an indicator of COS or schizophrenia that occurs in adulthood.